The story of living in spite of melanoma, metastasis, vaccines, anti-PD-1, lung removal, and stereotactic radiation. The story of life with family and friends. {Posts under ~ Sew Chaotically, Travel Chaotically, and Chaotic Cookery also housed within! A girl's gotta have fun!}

About Me

Who am I? That is a question the rest of you could probably answer better than I. I am a wife, mother, daughter, sister, friend, pediatric nurse practitioner, cook, teacher, gardener, lover of words and music, occasional seamstress, and homemaker. I do have a couple of talents of questionable merit: I can create a decent meal in less than 30 minutes. I can feed and/or soothe almost any baby. And I can remember practically any song I've ever heard. For the rest, I'd rather those who know me decide.

Thursday, November 17, 2016

BRAF/MEK combined with immunotherapy!!!

I thought this was a very
informative article regarding BRAF inhibitors, MEK inhibitors...what
we've learned and where research is looking with those drugs.Combination therapy with BRAF and MEK inhibitors for
melanoma: latest evidence and place in therapy.
Eroglue and Ribas. Ther Adv Med Onc. Jan 2016.

Treatment
with BRAF inhibitors such as vemurafenib or dabrafenib in patients with
advanced BRAFV600 mutated melanoma has shown objective tumor responses in
approximately half of the patients. However, the duration of responses is
limited in a majority of these patients, with progression-free survival rates
around 6 months due to tumor progression from development of acquired
resistance. Preclinical studies have suggested that concurrent inhibition of
the BRAF kinases and MEK of the mitogen-activated protein kinase (MAPK) pathway
could decrease MAPK-driven acquired resistance, resulting in longer duration of
responses, higher rate of tumor responses, and a decrease in the cutaneous
toxicities observed from paradoxical MAPK pathway activation with BRAF
inhibitor monotherapy. This review provides an overview of the currently
available clinical trial data on BRAF and MEK inhibitors together and in
combinations with other therapeutic agents.

The article goes
on to report: "About one half of melanoma patients
carry the BRAF V600E mutation. BRAF
inhibitors illicit 48-59% response rates in those patients. However, duration
of response is limited in most patients with a median PFS of 5-7 months
“although a minority can last for over 5 years”. BRAF inhibitors combined with MEK inhibitors
improved things further with decreased side effects and increased PFS,
amounting to 11-12 months depending on the combo. It also reviews the importance of
intermittent dosing as opposed to continuous therapy with BRAFi in order to
delay resistance. Other drugs combined
with BRAF/MEK , like heat shock protein 90 (HSP90) inhibitors, like XL88 can
overcome resistance. There are also
plans for additional studies using a triple therapy approach.

BRAF/MEK has provided
response rates of up to 70% in trials but with limited durability of that
response, researchers are looking at combining those drugs with checkpoint
inhibitors like ipi, anti-PD1, or anti-PD-L1.
When dabrafenib, trametinib and ipi were combined patients experienced
colitis with perforation. So that arm
was stopped, though the ipi and dabrafenib arm is ongoing. Another trial is currently looking at
dabrafenib, trametinib and anti-PD-L1 (MEDI4736). So far, the ratties are demonstrating a 69% ORR
and 16 of 18 patients have an ongoing response."